PNKD Gene - Paroxysmal Nonkinesigenic Dyskinesia
PNKD: A key regulator in paroxysmal movement disorders and neuronal signaling
Gene Information Card
| Symbol | PNKD |
|---|---|
| Full Name | Paroxysmal Nonkinesigenic Dyskinesia |
| Gene Type | Protein coding |
| Chromosomal Location | 2q35 |
| NCBI Gene ID | 25953 ncbi.nlm.nih.gov/gene/25953 |
| Ensembl ID | ENSG00000115977 |
| UniProt ID | Q8N490 |
| OMIM ID | 609023 |
| HGNC ID | 9153 |
| Aliases | FKSG22, MR-1, PNKD1 |
Description
The PNKD gene encodes a protein involved in the regulation of neuronal excitability. Mutations in this gene are associated with paroxysmal nonkinesigenic dyskinesia (PNKD), a disorder characterized by sudden, involuntary movements triggered by stress, caffeine, or alcohol. The protein is thought to modulate synaptic transmission and ion channel function.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Paroxysmal Nonkinesigenic Dyskinesia (PNKD) | Missense mutations in PNKD lead to altered protein function, causing abnormal neuronal firing and movement episodes. | OMIM #609023; ClinVar |
| Episodic Ataxia (possible overlap) | Rare variants may affect cerebellar function, though evidence is limited. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebellum) | 12.5 | Medium |
| Brain (cortex) | 8.3 | Low |
| Testis | 6.7 | Low |
| Heart | 4.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 10.1 | Neuronal model |
| HEK293 (embryonic kidney) | 3.5 | Low expression |
| U-87 MG (glioblastoma) | 7.8 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.20C>T (p.Ala7Val) | Missense | Common in PNKD families | Alters protein stability and function |
| c.26G>A (p.Gly9Arg) | Missense | Rare | Impaired synaptic regulation |
| c.97C>T (p.Arg33Trp) | Missense | Reported in sporadic cases | Unknown functional effect |
Mutation functional classification
Loss of Function (LOF)
Not established; most mutations are missense with unclear effect on protein activity.
Gain of Function (GOF)
Hypothesized for p.Ala7Val, which may enhance neuronal excitability.
Dominant Negative (DN)
Possible for p.Gly9Arg, interfering with wild-type protein function.
View complete mutation data：
Gene Ontology (GO)
| • chemical synaptic transmission (GO:0007268) | • synapse (GO:0045202) |
| • protein binding (GO:0005515) | • plasma membrane (GO:0005886) |
Pathways
• Synaptic vesicle cycle (Reactome: R-HSA-421837)
• Neurotransmitter release cycle (Reactome: R-HSA-112310)
Protein Summary
The PNKD protein (UniProt Q8N490) is a 385-amino acid membrane-associated protein predominantly expressed in the brain. It contains a conserved domain of unknown function (DUF) and is implicated in modulating synaptic vesicle trafficking and ion channel activity. Mutations in PNKD are linked to paroxysmal dyskinesia, likely through altered neuronal signaling.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PNKD Knockout HEK293 Cell Line | EDJ-KQ3575 | Human | 25953 | Details Get a Quote |
| PNKD Knockout A-549 Cell Line | EDJ-KQ25457 | Human | 25953 | Details Get a Quote |
| PNKD Knockout HCT 116 Cell Line | EDJ-KQ25458 | Human | 25953 | Details Get a Quote |
| PNKD Knockout HeLa Cell Line | EDJ-KQ25459 | Human | 25953 | Details Get a Quote |
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